Pharmacokinetics and bone formation by BMP-2 entrapped in polyethylenimine-coated albumin nanoparticles |
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| Authors: | Sufeng Zhang Michael R. Doschak Hasan Uluda? |
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| Affiliation: | 1. Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada;2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada;3. Department of Biomedical Engineering, Faculty of Medicine, University of Alberta, Edmonton, AB, Canada;1. School of Environment, Henan Normal University, Xinxiang, Henan 453007, PR China;2. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, PR China;1. Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, South Korea;2. Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, South Korea;3. Glass Research Department, National Research Center, Cairo 12622, Egypt;4. Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 330-714, South Korea;1. Clinical Engineering, Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, UK;2. Drug Delivery and Tissue Engineering, Centre for Biomolecular Sciences, University of Nottingham, UK;3. Biophysics and Surface Analysis, Boots Science Building, University of Nottingham, UK;1. Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA;2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive NW, Atlanta, GA 30332, USA;3. Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA;4. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive NW, Atlanta, GA 30332, USA;1. Department of Orthopaedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;2. MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China;3. Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310030, China;1. The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China;2. Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China;3. Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China |
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| Abstract: | The osteoinductive growth factor, bone morphogenetic protein-2 (BMP-2), is capable of inducing de novo bone formation after implantation. A nanoparticulate (NP) system was developed for BMP-2 delivery based on NPs fabricated from bovine serum albumin (BSA) and stabilized by polyethylenimine (PEI) coating. In this study, the pharmacokinetics and osteoinductivity of BMP-2 delivered with different BSA NP formulations were determined by subcutaneous implantation in rats. A 7-day pharmacokinetics study showed that PEI coating on NPs effectively reduced the initial burst release of BMP-2 and prolonged the BMP-2 retention at implantation site. However, the uncoated BMP-2 NPs (BMP-2 loading of 1.44% w/w) were able to induce a robust ectopic bone formation, while no bone formation was found by the BMP-2 NPs coated with PEI. The toxicity of the PEI used for NP coating was determined to be the reason for lack of osteoinduction. Increasing BMP-2 loading (up to 5.76% w/w) was then employed to formulate NPs with lower PEI content; the higher BMP-2 loading was found to better promote induction of de novo bone. Our findings indicated that PEI coating on BSA NPs was effective for controlling BMP-2 release from NPs, but the toxicity of cationic PEI was a concern for the osteoinductive activity, which should be alleviated by further optimization of NP formulations. |
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